Each year, numerous individuals are infected with different strains and types of influenza virus. Infants, the elderly, those without adequate health care and immuno-compromised persons, and, in some cases, otherwise healthy adults who require protection from viral diseases without causing an immune response associated with a “cytokine-storm,” are all at risk of death from such infections. Compounding the problem of influenza infections, novel influenza strains evolve readily and can spread amongst various species, thereby necessitating the continuous production of new vaccines. Although numerous vaccines capable of inducing a protective immune response specific for different influenza virus strains have been produced for over 50 years and include whole virus vaccines, split virus vaccines, surface antigen vaccines and live attenuated virus vaccines. New influenza vaccines are constantly required because of 1) mutations, 2) resortment of components between various strains, and 3) the continual emergence (or re-emergence) of different influenza strains.
Appropriate formulations of peptide heteroconjugates can stimulate and produce a systemic immune response. Peptide heteroconjugate technology has provided the ability to produce vaccines using genetic engineering (recombinant vaccines). Such vaccines are typically created using antigenic moieties of the newly emergent virus strains when polypeptides and polynucleotides of novel, newly emergent, or newly re-emergent virus strains are desired. The focus on most current vaccines is not on conserved proteins and, especially, essential regions of such conserved proteins or conserved regions of less conserved proteins, such as the neuramidinase (NA or N) or hemagglutin (HA or H) molecules found between various strains (e.g., H1N1, H1N5, H3N1, H1N9), but is more focused on the strain differences for these HA and NA molecules that account for the differences in H1 from H2, etc. or N1 from N2, etc.
One of these influenza epitopes is found in the 1918 “Spanish Influenza” pandemic. The 1918 Spanish influenza is similar to 2009 California H1N1 influenza, because there can be two initial mild waves late in a influenza season, and in 1918 and 1919 followed by a subsequent seasons with a severe, deadly disease with the propensity for affecting healthy immune systems with a cytokine storm (hypercytokinemia). However, the production of too many pro-inflammatory cytokines is thought to be a cause of death in the case of Type A influenza (e.g., H1N1), which is not addressed by current vaccines. A cytokine storm is caused by excessive amounts of pro-inflammatory cytokines and tends to occur in patients with stronger immune “robust” systems. There is a need for a formulation and a method of vaccination to combat a forthcoming deadly pandemic and to protect against new strains of type A influenza. These influenza viruses can be the most deadly for people in their prime, rather than affecting only the very young, the very old, or the most severely immunocompromised. There is also a need for an effective protective immune response without causing excessive amounts of pro-inflammatory cytokines that is effective against Type A influenza.